Clinical Trial Results:
A study to assess near infrared laparoscopy with indocyanine green (ICG) for intraoperative lymphatic imaging and sentinel lymph node identification during standard surgical resection for colonic cancer
Summary
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EudraCT number |
2012-000424-18 |
Trial protocol |
GB |
Global end of trial date |
26 Oct 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Mar 2016
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First version publication date |
20 Mar 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ICTUC/32/2012
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Imperial College London
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Sponsor organisation address |
Room 215 Level 2, Medical School Building Norfolk Place, London, United Kingdom, W2 1PG
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Public contact |
Professor Robin Kennedy, St Marks Hospital - North West London Hospitals NHS Trust, 44 20 8235 4055, robin.kennedy@nhs.net
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Scientific contact |
Professor Robin Kennedy, St Marks Hospital - North West London Hospitals NHS Trust, 44 20 8235 4055, robin.kennedy@nhs.net
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Nov 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Oct 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Oct 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To establish whether it is possible to identify the first order draining mesocolic lymph nodes (sentinel lymph node(s) (SLNs) in patients with suspected T1 and T2 colonic cancer, using ICG, a fluorescent mapping agent, and a laparoscopic near infrared imaging (NIR) system.
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Protection of trial subjects |
During protocol development two main areas of risk were identified as requiring specific inclusion/exclusion criteria:
1. Risk of allergic (analphylactic or anaphylactoid) reaction which is deemed to be less than 1 in 10. This risk was highlighted in the protocol and all participants were asked about any prior exposure to the agent or reaction to iodine dyes and shellfish. In addition patient’s notes were thoroughly reviewed by a member of the research team as part of the patient’s eligibility assessment.
2. Adverse effects of pregnancy. A pregnancy test was performed in all women of childbearing potential as part of the assessment for eligibility and those who tested positive were excluded from the trial.
In addition a risk of colonic perforation (1/2000) related to the endoscopy procedure was highlighted. The procedure, was essential in order to inject the tracer agent and therefore the risk was minimized by effective bowel preparation and ensuring that this examination was performed by an experienced endoscopist. Finally it was stated the study will add 30 minutes to the total operative time. This was considered acceptable by the senior members of the investigative team and would have minimal risk to the patient.
An independent, combined Trial Steering Committee/Data Monitoring Committee was convened to oversee the trial.
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Background therapy |
There were no protocol-specified background therapies. Concomitant medications could be prescribed at the treating physicians discretion, with the exception of prohibited medications described in the study protocol. Concomitant medications (and the reason for the medication) were recorded in the study database for the period 4-weeks prior to starting study treatment until the patient's last study visit. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Jun 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
12
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From 65 to 84 years |
16
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85 years and over |
2
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Recruitment
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Recruitment details |
The study recruited all 30 patients in one UK site. This site opened to recruitment on 26/06/2016 and the first and last patient consent was on 30/08/2013 and 10/09/2015 respectively. | ||||||
Pre-assignment
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Screening details |
In total 145 patients were screened for the study, 111 were excluded on inclusion / exclusion criteria. The remaining 34 were approached to participate. Of those 34, 4 patients declined and 30 patients were consented to the study. Each patient consented met all inclusion and no exclusion criteria and was therefore enrolled onto the trial. | ||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
Not Applicable
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Arms
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Arm title
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Interventional Arm | ||||||
Arm description |
There is only 1 arm in this study. All patients were in the interventional arm and received indocyanine green dye during their surgery so lymphatic imaging and sentinel lymph node identification could be performed as defined in the protocol. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Indocyanine Green
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Submucosal use
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Dosage and administration details |
5 ml of the mapping agent (ICG) were injected endoscopically into the submucosa in three / four points around the tumour
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
T1/T2 Colon Cancer
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients with stage T1/T2 colon cancer at baseline
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End points reporting groups
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Reporting group title |
Interventional Arm
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Reporting group description |
There is only 1 arm in this study. All patients were in the interventional arm and received indocyanine green dye during their surgery so lymphatic imaging and sentinel lymph node identification could be performed as defined in the protocol. | ||
Subject analysis set title |
T1/T2 Colon Cancer
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with stage T1/T2 colon cancer at baseline
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End point title |
Average number of sentinel lymph nodes identified for patients where sentinel lymph nodes were identified [1] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Average number of sentinel lymph nodes identified for patients where sentinel lymph nodes were identified. This analysis was completed when the last patient had completed the trial.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Primary analysis was performed using a univariate methods. This method does not have an associated p-value. The EudraCT system would not allow statistical analysis details to be completed without entry of a p-value, however, this does not exist for this data set. Therefore we are unable to add statistical analysis details due to operational errors with the database. |
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No statistical analyses for this end point |
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End point title |
Average time to identification of lymphatic vessels in minutes [2] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Average time to identification of lymphatic vessels in minutes. This analysis was performed when the last patient had completed the trial.
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Primary analysis was performed using a univariate methods. This method does not have an associated p-value. The EudraCT system would not allow statistical analysis details to be completed without entry of a p-value, however, this does not exist for this data set. Therefore we are unable to add statistical analysis details due to operational errors with the database. |
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No statistical analyses for this end point |
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End point title |
Average time to Identification of lymph nodes [3] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Average time to Identification of lymph nodes. This analysis was completed when the last patient completed the trial.
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Primary analysis was performed using a univariate methods. This method does not have an associated p-value. The EudraCT system would not allow statistical analysis details to be completed without entry of a p-value, however, this does not exist for this data set. Therefore we are unable to add statistical analysis details due to operational errors with the database. |
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No statistical analyses for this end point |
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End point title |
Number of patients with aberrant nodal drainage. [4] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Number of patients with aberrant nodal drainage. This analysis was performed when the last patient had completed the trial.
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Primary analysis was performed using a univariate methods. This method does not have an associated p-value. The EudraCT system would not allow statistical analysis details to be completed without entry of a p-value, however, this does not exist for this data set. Therefore we are unable to add statistical analysis details due to operational errors with the database. |
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No statistical analyses for this end point |
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End point title |
Number of patients in which sentinel lymph nodes were identified [5] | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Number of patients in which sentinel lymph nodes were identified as assessed when the last patient had completed the study.
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Primary analysis was performed using a univariate methods. This method does not have an associated p-value. The EudraCT system would not allow statistical analysis details to be completed without entry of a p-value, however, this does not exist for this data set. Therefore we are unable to add statistical analysis details due to operational errors with the database. |
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No statistical analyses for this end point |
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End point title |
Sensitivity of sentinel node findings | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed after the last patient had completed the study.
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Notes [6] - Diagnostic test results include 3 patients with no SLNs identified. Patients assumed to be negative. [7] - Diagnostic test results include 1 patient with no SLNs identified. Patient assumed to be negative. |
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No statistical analyses for this end point |
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End point title |
Specificity of sentinel node findings | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed when the last patient completed the study.
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Notes [8] - Diagnostic test results include 3 patients with no SLNs identified. Patients assumed to be negative. [9] - Diagnostic test results include 1 patient with no SLNs identified. Patient assumed to be negative. |
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No statistical analyses for this end point |
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End point title |
Positive predictive value of sentinel node findings | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed when the last patient completed the study.
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Notes [10] - Diagnostic test include 3 patients with no SLN identified. Patients assumed negative |
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No statistical analyses for this end point |
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End point title |
Negative predictive value of sentinel node findings | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed when the last patient had completed the study.
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Notes [11] - Diagnostic test results include 3 patients with no SLNs identified. Patients assumed to be negative. [12] - Diagnostic test results include 1 patient with no SLNs identified. Patient assumed to be negative. |
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No statistical analyses for this end point |
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End point title |
Accuracy of sentinel node findings | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed when the last patient has completed the study.
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Notes [13] - Diagnostic test results include 3 patients with no SLNs identified. Patients assumed to be negative. [14] - Diagnostic test results include 1 patient with no SLNs identified. Patient assumed to be negative. |
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No statistical analyses for this end point |
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End point title |
Patients with aberrant sentinel nodes | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed after the last patient had completed the study.
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No statistical analyses for this end point |
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End point title |
Patients with positive aberrant nodes | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
This analysis was performed after the last patient had completed the study.
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No statistical analyses for this end point |
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End point title |
Number of lymph nodes identified per patient | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Average number of lymph nodes identified for patients. This analysis was completed when the last patient had completed the trial.
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No statistical analyses for this end point |
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End point title |
Number of patients with positive nodes | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Percentage of patients with positive nodes. This analysis was completed when the last patient had completed the trial.
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No statistical analyses for this end point |
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End point title |
Number of patients with positive sentinel nodes | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Percentage of patients with positive sentinel nodes. This analysis was completed when the last patient had completed the trial.
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events were collected from the time a patient signed informed consent until the end of followup.
AEs were followed-up according to local practice until the event has stabilised or resolved, or until
the last follow-up visit, whichever was sooner
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Adverse event reporting additional description |
AEs were reviewed at every patient visit.
AEs we assessed for severity (NCI CTCAE v4.03) and causality by the local PI; the CI provided an assessment for SAEs. All AEs were recorded in the study EDC system.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18
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Reporting groups
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Reporting group title |
Interventional Arm
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Reporting group description |
All patients that received at least one dose of the IMP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |